Complete human CD1a deficiency on Langerhans cells due to a rare point mutation in the coding sequence


To the Editor: The family of CD1 molecules is structurally similar to MHC class I molecules, but the 2 protein families mediate fundamentally different immune functions. MHC class I molecules present peptides to T cells, whereas CD1 molecules present lipids to natural killer T cells and other CD1-restricted T cells. CD1a is highly expressed on human Langerhans cells (LCs), a specialized mononuclear phagocyte that is prevalent in the epithelial cell layer of the skin and mucosal surfaces. Epidermal LCs can function as classical antigen-presenting cells (APCs) to induce naive T-cell responses in draining lymph nodes, but also have a regulatory function in the skin via local induction of regulatory T cells and maintenance of epithelial barrier integrity. Human dermal dendritic cells (DCs) also express CD1a, but in much lower amounts compared with LCs. CD1a dermal DCs, which coexpress CD1c, have been shown to efficiently stimulate CD4 and CD8 T cells in vitro. However, immune deficiencies due to selective CD1a defects have not been previously described, and it has proved difficult to dissect the specific role of CD1a in immune regulation. During the course of a clinical study that involvedanalysis ofAPC subsets in human skin biopsies by flow cytometry, we identified a healthy Vietnamese individual, donor 007, who showed complete absence of CD1a expression on skinAPCs (Fig 1,A). This case presented an opportunity to study the biological significance of CD1a expression. To check whether LCs were absent altogether in donor 007, we obtained a second skin biopsy, separated the epidermis from the underlying structures, and stained the epidermal tissues with antibodies binding to CD1a and to HLA-DR. Donor 007 LCs displayed intense HLA-DR staining with typical dendritic morphology, but CD1a staining was minimal (Fig 1, B). We next addressed whether the CD1a deficiency represented a generic expression defect, using monocyte-derived dendritic cells (moDCs) as a model. In keeping with our earlier observations, moDCs from donor 007 showed no surface CD1a expression by flow cytometry or immunohistochemistry (see Fig E1, A, in this article’s Online Repository at, in contrast to moDCs derived from a normal healthy control donor. Staining with other anti-human CD1a clones, OKT6 and NA1/34-HLK, showed the same result as staining with clone HI149 (see Figs E2 and E3 in this article’s Online Repository at www. In addition, no costain with early endosome antigen-1 and CD1awas observed, excluding CD1a accumulation in early endosomes in donor 007 (Fig E1, B). To address whether the CD1a defect was caused by a mutation in the CD1a gene, we invited the parents and all 4 siblings of


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